Journal of Hepatocellular Carcinoma最新文献

{"title":"Gut Microbiota in Hepatocellular Carcinoma: Etiology-Specific Evidence, Mechanisms, and Translational Challenges.","authors":"Xiaohuan Guan","doi":"10.2147/JHC.S636365","DOIUrl":"10.2147/JHC.S636365","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) usually develops in patients with chronic liver disease and remains a major cause of cancer-related death worldwide. Increasing evidence suggests that dysbiosis of the gut microbiota is related to hepatocarcinogenesis through the gut-liver axis. Patients with HCC often show enrichment of pro-inflammatory or endotoxin-producing bacteria and loss of short-chain fatty acid-producing and barrier-protective taxa. These changes may increase intestinal permeability and microbial translocation and may contribute to chronic hepatic inflammation, immune disturbance, and metabolic changes. Lipopolysaccharide, secondary bile acids, and trimethylamine-N-oxide are among the microbial products that may connect intestinal dysbiosis with liver fibrosis and tumor progression. Clinical studies have also examined microbial signatures for early HCC detection, risk stratification, recurrence, and response to immune checkpoint inhibitors. However, most cohorts are small and differ in etiology, region, medication exposure, and sequencing method. Animal studies indicate that antibiotics, probiotics, fecal microbiota transplantation, and diet can change tumor development or treatment response, but direct clinical evidence in HCC remains limited. This review summarizes the compositional, mechanistic, and clinical evidence and discusses the present status of microbiota-targeted strategies in HCC.</p>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"13 ","pages":"636365"},"PeriodicalIF":3.9,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13615818/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149061518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"miR-139-5p Targets CENPM to Suppress EMT and Malignant Progression of Hepatocellular Carcinoma via Regulating the Akt/mTOR Pathway and β-Catenin Nuclear Translocation.","authors":"Aihui Fan, Xiaomin Zhang, Hongjing Cui, Xianling Gong, Zhanping Gou, Chong Yan, Yanfei Guan, Shengchun Wang, Jingyi Zheng, Wanyi Li, Linghui Dian, Jilun Cheng","doi":"10.2147/JHC.S588389","DOIUrl":"10.2147/JHC.S588389","url":null,"abstract":"<p><strong>Purpose: </strong>This study aims to screen key miRNA/mRNA axes associated with hepatocellular carcinoma (HCC), and then conduct functional validation and mechanistic exploration, thereby offering novel clues for screening HCC-targeted therapeutic candidates.</p><p><strong>Methods: </strong>Bioinformatics analysis was performed to identify key HCC-related miRNA/mRNA axes. The direct interaction between hsa-miR-139-5p and centromere protein M (CENPM) was verified via a dual-luciferase reporter (DLR) assay. We carried out colony formation, Transwell and in vivo xenograft assays to validate the biological functions of the hsa-miR-139-5p/CENPM axis. The underlying mechanism of this axis was further explored via in vitro cellular experiments. The Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA-LIHC) cohort was used for prognostic evaluation of this axis.</p><p><strong>Results: </strong>Six key HCC-related miRNA/mRNA regulatory axes were screened out. The hsa-miR-139-5p/CENPM axis was selected for further validation. DLR assay confirmed that hsa-miR-139-5p directly targeted CENPM. Sole overexpression of hsa-miR-139-5p significantly downregulated CENPM protein levels, and suppressed in vitro cell colony formation, migration and invasion, as well as in vivo growth of subcutaneous HCC xenografts. Notably, simultaneous overexpression of CENPM could fully rescue the tumor-suppressive phenotypes induced by hsa-miR-139-5p overexpression. In contrast, sole overexpression of CENPM markedly promoted HCC cell malignant behaviors and subcutaneous xenograft growth, while concurrent transfection of hsa-miR-139-5p could attenuate these oncogenic effects driven by CENPM overexpression. Mechanistically, hsa-miR-139-5p restrained the activation of the Akt/mTOR pathway and inhibited nuclear translocation of β-catenin to suppress epithelial-mesenchymal transition (EMT) by targeting CENPM in HCC cells. The hsa-miR-139-5p^high/CENPM^low subgroup had significantly better survival outcomes than the hsa-miR-139-5p^low/CENPM^high subgroup.</p><p><strong>Conclusion: </strong>hsa-miR-139-5p targeted CENPM to suppress EMT and malignant progression of HCC via regulating the Akt/mTOR pathway and β-catenin nuclear translocation. The combined expression pattern of hsa-miR-139-5p and CENPM correlated significantly with HCC patient prognosis. Our findings offer new evidence for HCC prognostic stratification and targeted intervention candidate screening.</p>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"13 ","pages":"588389"},"PeriodicalIF":3.9,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13615298/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149061503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Large Language Models for Preoperative Microvascular Invasion Prediction in Hepatocellular Carcinoma: A Multicenter Comparison with Radiologists and Treatment Outcomes.","authors":"Ru Wen, Xuefeng Li, Fengxi Chen, Yujie Jiang, Chunxia Zhu, Huarong Zhang, Ping Cai, Wei Chen, Xiaoming Li","doi":"10.2147/JHC.S622973","DOIUrl":"10.2147/JHC.S622973","url":null,"abstract":"<p><strong>Background: </strong>Preoperative prediction of microvascular invasion (MVI) in hepatocellular carcinoma (HCC) is critical for prognosis but challenging. This study evaluated the performance of large language models (LLMs) for MVI prediction compared with radiologists with varying levels of experience and explored the association of model-predicted MVI with recurrence and treatment outcomes.</p><p><strong>Materials and methods: </strong>In this retrospective multicenter study, 602 patients with pathologically confirmed HCC who underwent preoperative MRI and surgical resection were included. GPT-4o and DeepSeek-R1, prompted in English and Chinese using radiology report narratives and predefined MRI features, were compared with six radiologists using histopathology as the reference standard. An independent cohort of 135 patients who underwent radiofrequency ablation (RFA) was included for treatment-outcome analyses. Prediction performance was assessed using diagnostic accuracy and the area under the curve (AUC).</p><p><strong>Results: </strong>GPT-4o (English input) achieved 75.6% accuracy, outperforming residents (59.3%, P < 0.001) and attendings (66.7%, P < 0.001), and was comparable to senior radiologists (74.2%, P = 1.000). DeepSeek-R1 (Chinese input) achieved the highest accuracy (81.2%), outperforming all radiologists (P < 0.05). Residents and attendings showed high sensitivity but relatively low specificity, whereas senior radiologists demonstrated a more balanced performance; while DeepSeek-R1 showed better specificity (up to 94.2%, P < 0.001). LLMs performance were relatively stable across tumor sizes, whereas accuracy among less-experienced radiologists improved with tumor size. AUCs for LLMs (GPT-4o: 75.4%; DeepSeek-R1 Chinese: 80.1%) were superior or comparable to those of radiologists (61.8%-74.5%). Stacking ensemble-predicted MVI-positive status was associated with shorter time-to-recurrence (TTR) in both small (≤3 cm, P = 0.039) and large (>3 cm, P = 0.001) tumors, and with better outcomes following anatomical rather than non-anatomical resection (≤3 cm, P = 0.021; >3 cm, P < 0.001). After propensity score matching, surgical resection was associated with longer TTR than RFA in the model-predicted MVI-positive subgroup, but not in the MVI-negative subgroup.</p><p><strong>Conclusion: </strong>LLMs, particularly DeepSeek-R1 and GPT-4o, demonstrated diagnostic performance for preoperative MVI prediction comparable to or better than that of senior radiologists, with relatively stable performance across tumor sizes and potential value for recurrence-risk stratification and treatment planning.</p>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"13 ","pages":"622973"},"PeriodicalIF":3.9,"publicationDate":"2026-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13601009/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149039090","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multidisciplinary Treatment for Liver Cancer in China: A Cross-Sectional Survey of Practices, Gaps and Future Directions.","authors":"Wei Wang, Wei Jia, Dao-Cheng Zhan, Heng-Jun Wu, FanZheng Meng, Shu-Geng Zhang, Rui-Peng Song, Jia-Bei Wang, Yao Liu, Ji-Zhou Wang, Da-Long Yin, Hui-Chuan Sun, Lianxin Liu","doi":"10.2147/JHC.S617462","DOIUrl":"10.2147/JHC.S617462","url":null,"abstract":"<p><strong>Objective: </strong>To systematically evaluate the current status of the establishment and operation of multidisciplinary treatment (MDT) for liver cancer in China, identify key bottlenecks, and provide a scientific basis for promoting the transition of MDT from \"demonstration and exploration\" to \"standardized construction\".</p><p><strong>Methods: </strong>This study adopted a cross-sectional survey design to systematically investigate the current establishment and operational status of MDT for liver cancer in China. A total of 1,073 hospitals across 31 provincial-level administrative regions in China were selected as study sites. The study participants included 1,279 clinicians and relevant medical staff directly engaged in the clinical practice of liver cancer MDT.</p><p><strong>Results: </strong>A total of 1,279 questionnaires were distributed, with 1,073 valid responses collected (validity rate: 83.89%). The results revealed the following characteristics of liver cancer MDT in China: (1) Organizational Structure: 51.35% of hospitals had implemented liver cancer MDT, with 24.14% establishing fixed teams. The predominant model was department-led (65.25%); (2) Clinical Practice: Annual case discussions showed a polarized distribution (≤50 cases: 41.70%; >200 cases: 16.99%). A majority (90.73%) recognized MDT's significant impact on clinical decision-making, while 83.01% of respondents, based on their subjective experience, held the perception that MDT might be associated with survival improvement in patients; (3) Quality Control Systems: 79.92% of hospitals had basic quality control mechanisms, but only 2.96% had independent quality control departments. Information technology infrastructure required improvement (only 35.91% achieved data platform integration); (4) Key Bottlenecks: Insufficient policy support (41.18%), staffing challenges (19.92%), and scheduling difficulties (13.82%).</p><p><strong>Conclusion: </strong>While liver cancer MDT has been preliminarily established in hospitals in China, challenges such as regional disparities, hospital-level gradient, weak quality control, and inadequate IT infrastructure persist. A tripartite strategy-incorporating tiered healthcare delivery, standardized protocols, and technological innovation-is recommended to achieve a qualitative transformation and support the \"Healthy China 2030\" initiative in liver cancer prevention and treatment.</p>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"13 ","pages":"617462"},"PeriodicalIF":3.9,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13594519/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149025038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Current Perspectives on the Use of Adjuvant Pembrolizumab for Hepatocellular Carcinoma.","authors":"Anna Mingazzini, Daniel Riado Minguez, Ylenia Babini, Elia Gigante, Mohamed Bouattour","doi":"10.2147/JHC.S613651","DOIUrl":"10.2147/JHC.S613651","url":null,"abstract":"<p><p>Despite implementation of surveillance in at-risk populations and the availability of potentially curative treatment such as resection or ablation, recurrence of hepatocellular carcinoma (HCC) remains a frequent clinical challenge driven by both occult residual disease and de novo carcinogenesis, and can have a major impact on patients' quality of life. Current evidence does not support adjuvant therapy after curative treatment in early-stage HCC, and active surveillance remains the standard of care. Following the historical failure of adjuvant tyrosine kinase inhibitors, the integration of immune checkpoint inhibitors (ICIs) in advanced HCC treatment has renewed interest in their application in the curative-intent setting, particularly for their potential to eradicate microscopic residual disease. Preliminary evidence on adjuvant PD-1-based combinations supported the plausibility of immune modulation, although most of today's evidence derives from retrospective heterogeneous cohorts including multiple anti-PD-1 agents. Pembrolizumab, a monoclonal anti-PD-1 antibody that restores antitumor T-cell activity, has recently attracted growing interest on the postoperative management of early- and intermediate-stage HCC. KEYNOTE-937 was a Phase III trial comparing pembrolizumab to placebo after curative treatment whose results failed to demonstrate improvement in recurrence-free survival. This outcome suggested that postoperative PD-1 blockade alone may be insufficient to prevent tumor relapse, especially without proper selection on residual disease or treatment sensitivity. Conversely, pembrolizumab-based strategies administered in the neoadjuvant or perioperative setting remain underexplored. As persistence of tumor antigens with intact tumor burden may offer a more favorable immunological context, this setting may be better suited for enhancing antitumor immune priming. In conclusion, the negative findings of KEYNOTE-937 provide a useful foundation for refining future PD-1-based strategies in HCC. Progress will require integration of molecular residual disease assessment with pathological risk stratification and liver disease etiology, in order to identify patients with immunologically targetable residual disease who may derive meaningful benefit from adjuvant pembrolizumab.</p>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"13 ","pages":"613651"},"PeriodicalIF":3.9,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13589979/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149012578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bibliometric Analysis of Gut Microbiota and Hepatocellular Carcinoma: Research Trends and Frontiers.","authors":"Chengpu Zhao, Xiangcheng Hu","doi":"10.2147/JHC.S631427","DOIUrl":"10.2147/JHC.S631427","url":null,"abstract":"<p><strong>Background: </strong>The gut microbiota plays a pivotal role in hepatocellular carcinoma (HCC) pathogenesis via the gut-liver axis. Existing gut microbiota-HCC studies are mostly narrative, with three critical knowledge gaps: lack of data-driven global research mapping, unclear staged field evolution, and insufficient quantitative identification of research frontiers. This bibliometric study aims to fill these gaps by systematically quantifying field-wide research trends, hotspots and frontiers.</p><p><strong>Methods: </strong>A bibliometric analysis was performed including 1383 English original and review articles (2010-2026) retrieved from WOSCC and PubMed. Bibliometrix, VOSviewer, and CiteSpace were applied to conduct co-authorship and co-citation analysis for countries, institutions and authors, keyword co-occurrence, clustering and burst detection. Bibliometric metrics including Bradford's law, Lotka's law, h-index, g-index and m-index were applied to analyse publication trends, research outputs, journal-author features and research hotspots.</p><p><strong>Results: </strong>Annual publications increased by 26.95%, with 22.49% international collaboration. China led output (679 papers) but with lower citation impact, while the USA (299 papers) dominated high-quality research. Close domestic academic connections were observed within Chinese and US institutional clusters, whereas cross-national cooperation between Chinese and US institutions remained limited. Top productive institutions were mainly from China, while US institutions exhibited superior citation performance. Journal distribution followed Bradford's law, with Frontiers-series open-access journals dominating the core journal zone. Keyword clustering revealed three successive macro research phases: early association studies (2010-2017), gut-liver axis mechanism exploration (2018-2021), and current focus on microbial metabolites and immunotherapy modulation (2022-2026).</p><p><strong>Conclusion: </strong>The field shows rapid expansion with a China-USA dual research high-output research pattern, shifting toward microbial metabolites and microbiota-targeted immunotherapy. This work provides comprehensive quantitative data to compensate for missing panoramic and staged analyses in prior literature; future advances rely on causal mechanism verification, large-scale clinical trials and strengthened international collaboration.</p>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"13 ","pages":"631427"},"PeriodicalIF":3.9,"publicationDate":"2026-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13584948/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148990235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of week-2 Contrast-Enhanced Ultrasound Perfusion Changes with Response to Lenvatinib Plus PD-1 Inhibitors in Unresectable Hepatocellular Carcinoma: A Retrospective Exploratory Study.","authors":"Hang Su, Yang Gao, Song Zhang, Pei-Hao Wen","doi":"10.2147/JHC.S637139","DOIUrl":"https://doi.org/10.2147/JHC.S637139","url":null,"abstract":"<p><strong>Background: </strong>To explore whether early contrast-enhanced ultrasound (CEUS)-derived tumor perfusion changes were associated with subsequent response to Lenvatinib plus PD-1 inhibitors in unresectable hepatocellular carcinoma (HCC).</p><p><strong>Methods: </strong>This study included 74 patients with unresectable HCC treated with Lenvatinib plus PD-1 inhibitors in routine clinical practice retrospectively. Baseline and early on-treatment CEUS examinations at approximately 2 weeks after treatment initiation were analyzed to quantify tumor perfusion parameters. Objective response rate (ORR), disease control rate (DCR), duration of response (DoR), progression-free survival (PFS) and overall survival (OS) were study endpoints. Associations between CEUS findings and treatment outcomes were analyzed.</p><p><strong>Results: </strong>ORR of Lenvatinib plus PD-1 inhibitors among 74 patients with HCC was 33.8% (95% CI: 23.2-45.7%) and DCR was 73.0% (95% CI: 61.4-82.6%). Median DoR among the 25 responders was 8.7 months (95% CI: 7.39-10.01 months). After a median follow-up duration of 21.1 months, median PFS was 6.9 months (95% CI: 4.33-9.47 months) and median OS was 21.3 months (95% CI: 14.70-27.90 months). CEUS perfusion analysis showed that baseline tumor enhancement did not significantly differ between eventual responders and non-responders. In contrast, week-2 CEUS-derived perfusion changes, particularly percentage reduction in AUC, were associated with subsequent radiologic response. Using an exploratory cutoff of ≥35% AUC reduction, patients above this threshold showed longer PFS and OS than those below the threshold. These associations remained exploratory because the threshold was derived within a limited retrospective cohort. Treatment was generally well tolerated, no unexpected adverse events occurred, and there were no treatment-related deaths in this cohort.</p><p><strong>Conclusion: </strong>In this single-center retrospective exploratory cohort, week-2 CEUS-derived AUC reduction was associated with subsequent radiological response and survival outcomes in patients with unresectable HCC receiving Lenvatinib plus PD-1 inhibitors. These findings should be interpreted as hypothesis-generating and require prospective validation before CEUS-based perfusion changes can be used for clinical decision-making.</p>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"13 ","pages":"637139"},"PeriodicalIF":3.9,"publicationDate":"2026-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13580446/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148990198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FOLFOX-HAIC Plus Lenvatinib and Tislelizumab in Advanced Hepatocellular Carcinoma with Arteriovenous Fistulae: A Real-World Study.","authors":"Pengen Li, Shumin Fu, Xiao Wang, Yi Chen, Jianbing Wu, Weimin Jiang, Ye Mao","doi":"10.2147/JHC.S621670","DOIUrl":"10.2147/JHC.S621670","url":null,"abstract":"<p><strong>Background and aims: </strong>Patients with advanced hepatocellular carcinoma (HCC) complicated by arteriovenous fistula (AVF) often fail to benefit from conventional transarterial chemoembolization (TACE) because of the associated hemodynamic abnormalities, resulting in an extremely poor prognosis. This retrospective, single-center, single-arm study was conducted to preliminarily evaluate the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC) using the FOLFOX regimen in combination with lenvatinib and tislelizumab in this population of patients with unresectable/advanced HCC.</p><p><strong>Methods: </strong>A total of 51 patients with advanced HCC complicated by angiographically confirmed AVF, who were treated at our institution between December 2020 and May 2025, were retrospectively enrolled. All patients received the aforementioned triple-therapy regimen as first-line treatment. The primary endpoint was progression-free survival (PFS), while secondary endpoints included overall survival (OS), objective response rate (ORR), fistula closure rate, and safety.</p><p><strong>Results: </strong>The median PFS and OS were 9.67 months and 14.63 months, respectively. According to the modified Response Evaluation Criteria in Solid Tumors (mRECIST), the ORR and disease control rate (DCR) were 72.55% and 92.16%, respectively. The overall AVF closure rate was 87.2%, and time-dependent covariate Cox regression analysis identified fistula closure as an independent protective factor for OS. Treatment-related adverse events (TRAEs) were manageable, and no treatment-related deaths occurred.</p><p><strong>Conclusion: </strong>This real-world study demonstrates that FOLFOX-based HAIC combined with lenvatinib and tislelizumab is associated with a high AVF closure rate, favorable survival outcomes, and a manageable safety profile in patients with unresectable/advanced HCC complicated by AVF. This combination regimen may offer a feasible therapeutic strategy for this refractory patient population; Meanwhile, we anticipate that prospective controlled studies will further consolidate and extend the current findings, so as to establish their clinical value in a more comprehensive manner.</p>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"13 ","pages":"621670"},"PeriodicalIF":3.9,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13577175/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148976961","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pre-TACE CK-MB/CK Ratio as an Independent Prognostic Biomarker in Advanced Hepatocellular Carcinoma.","authors":"Weiguo Lu, Ying Lu, Yang Wang","doi":"10.2147/JHC.S621877","DOIUrl":"10.2147/JHC.S621877","url":null,"abstract":"<p><strong>Purpose: </strong>Primary liver cancer is a prevalent malignancy with a poor prognosis globally. Patients with advanced disease often undergo transarterial chemoembolization (TACE), yet simple and effective prognostic biomarkers are lacking. This study aimed to investigate the prognostic value of the serum creatine kinase isoenzyme MB to total creatine kinase (CK-MB/CK) ratio in patients with advanced primary liver cancer receiving TACE.</p><p><strong>Patients and methods: </strong>A single-center retrospective cohort study was conducted, enrolling 158 patients between January 2021 and September 2024. Based on a CK-MB/CK ratio cutoff of 1, patients were categorized into an abnormal group (n=52) and a normal group (n=106). Comparative analysis of baseline characteristics, Kaplan-Meier survival analysis, and Cox proportional hazards regression modeling were performed to assess the relationship between the CK-MB/CK ratio and overall survival (OS).</p><p><strong>Results: </strong>Patients in the abnormal group exhibited lower body mass index (BMI), lower rates of previous hepatectomy, higher levels of tumor markers (including AFP and CEA), and poorer liver function indices compared to the normal group. Kaplan-Meier analysis revealed a significantly shorter OS in the abnormal group (median OS: 15.0 months vs 32.5 months, log-rank P < 0.001). Multivariate Cox regression analysis confirmed that an elevated CK-MB/CK ratio was an independent risk factor for OS, with a hazard ratio of 3.895 (95% confidence interval: 1.946-7.79).</p><p><strong>Conclusion: </strong>This retrospective single-center study suggests that a CK-MB/CK ratio >1 may serve as an independent and easily accessible marker of poor prognosis in patients with advanced liver cancer undergoing TACE. Further validation in larger cohorts is needed. This marker is cost-effective and readily available in routine clinical practice, showing potential for risk stratification. When combined with D-dimer, it may provide a practical tool for clinical prognostic stratification.</p>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"13 ","pages":"621877"},"PeriodicalIF":3.9,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13571617/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148963342","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of Mitochondrial Dysfunction in Hepatocellular Carcinoma: From Pathogenesis and Drug Resistance to Targeted Therapeutic Strategies.","authors":"Siyu Zhao, Qian Liu, Jing Li, Shilei Zhang, Shuo Wan, Yuan Yang, Feng Jin, Biguang Tuo, Hai Jin","doi":"10.2147/JHC.S627932","DOIUrl":"10.2147/JHC.S627932","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) is characterized by high malignancy and widespread drug resistance at advanced stages, posing formidable challenges in clinical diagnosis and treatment. Mitochondrial dysfunction is a core driver of HCC initiation and drug resistance. However, how its plasticity dynamically regulates tumor growth under various conditions remains to be systematically elucidated. This review systematically delineates the critical roles of mitochondrial dysfunction in HCC pathogenesis, drug resistance, and targeted therapy. Regarding pathogenesis, we integrate four major pathways, namely aberrant oxidative phosphorylation (OXPHOS) coupled with mitochondrial DNA (mtDNA) mutations, glutamine metabolic reprogramming, oxidative stress imbalance, and dysregulated ferroptosis, to elaborate the molecular basis driving HCC malignant progression. In terms of drug resistance mechanisms, mitochondrial plasticity is highlighted as a central adaptive hub that synergistically promotes resistance through multifaceted mechanisms, including remodeling of the tumor immune microenvironment, dynamic regulation of OXPHOS levels, and modulation of ferroptosis sensitivity. With respect to therapeutic strategies, we summarize the current major intervention directions, encompassing ROS/OXPHOS modulators, inhibitors targeting mitochondrial metabolic enzymes and transporters, ferroptosis inducers, as well as nanodelivery systems and combination therapies. Of note, the efficacy of these interventions often depends on the mitochondrial phenotypic state of the tumor; single-target approaches tend to yield limited long-term benefits, whereas combination regimens or dynamic adjustments based on mitochondrial plasticity status hold greater promise for clinical application. Collectively, this review consolidates the evidence positioning mitochondrial dysfunction as a convergence point linking HCC progression, drug resistance, and targeted therapy, and proposes that \"targeting mitochondrial plasticity\" may represent a novel direction for overcoming drug resistance and achieving precision therapy, thereby providing a theoretical reference for future basic research and clinical translation.</p>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"13 ","pages":"627932"},"PeriodicalIF":3.9,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13571629/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148963347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}